Osmotic delivery capsules, commonly referred to as "osmotic pumps," function by virtue of walls which selectively pass water into the capsule reservoir. Absorption of water by the capsule through these walls is driven by a water-attracting agent in the capsule interior which creates osmotic pressure across the capsule wall. The water-attracting agent may be the beneficial agent itself whose controlled release is sought, but in most cases, it is a separate agent specifically selected for its ability to draw water, this separate agent being isolated from the beneficial agent at one end of the capsule. In either case, the structure of the capsule wall does not permit the capsule to expand, and as a result, the water uptake causes discharge of the beneficial agent through an orifice in the capsule at the same rate that water enters by osmosis.
The terms "osmotically effective" and "osmotically active" are used in the literature to characterize the water-attracting agent which drives the osmotic flow. Certain agents of this type are termed "osmagents," which denotes water-soluble compounds to which the capsule wall is not permeable. Osmotically effective agents which are polymeric species are termed "osmopolymers," which term denotes water-swellable polymers. Osmagents and osmopolymers may be used individually in a capsule or they may be present as a mixture of the two. In cases where the osmotically active agent is separated from the beneficial agent by a movable partition or piston, the osmotically active agent and the compartment in which it resides may be referred to as an "osmotic engine."
Many protocols or situations require, or would benefit from, an intermittent or pulsatile release of the beneficial agent from the capsule. This is true of a variety of drugs, medicaments and nutriments, in a range of environments extending from veterinary medicine to human drug administrations, and to hobby situations such as fish tanks. The reasons vary, and may address such needs as mimicking a natural intermittent physiological release, allowing for periods of restoration of certain body functions between administrations, or adhering to preestablished feeding protocols. One of many examples of situations in which intermittent drug administration is desirable is the administration of somatotropin to swine. Administering the drug in this manner may result in an increase in average daily gain by diminishing the suppression of feed intake, which suppression occurs when the drug is administered at a constant rate and remains at a high level in the bloodstream of the animal. In addition, the pulsed release may increase the therapeutic index of some drugs which would allow for a lower total dose in those cases. Another example is the feeding of fish while one is away on vacation. Other examples abound.
Included in the patent literature relating to pulsatile osmotic pumps is U.S. Pat. No. 4,777,049, issued Oct. 11, 1988 to Magruder, P. R., et al. The pulsatile effect in this patent is achieved by the inclusion of a modulating agent with the beneficial agent to be delivered. The modulating agent is selected on the basis of its solubility in the delivery medium relative to the beneficial agent, and the pulsatile effect results from one of the two falling below its saturation point, causing more of the other to go into solution and thereby be released. The number of pulses one may obtain in this manner is limited, however, and it is difficult to achieve periodic pulses. The system of U.S. Pat. No. 4,723,958, issued Feb. 9, 1989 to Pope, D. G., et al. achieves the pulsatile effect by alternating layers of beneficial agent with layers of inert material. As it is being released, however, the beneficial agent emerges at a slow rate. The system of U.S. Pat. No. 4,842,867, issued June 27, 1989 to Ayer, A. D., et al., is also a layered system, and is best intended for a low number of pulses. Layered systems are also disclosed by Wong, P. S. L., et al., U.S. Pat. No. 4,874,388, issued Oct. 27, 1989; Wong, P. S. L., et al., U.S. Pat. No. 4,957,494, issued Sept. 18, 1990; and Wong, P. S. L., et a., U.S. Pat. No. 5,023,088, issued June 11, 1991.
Devices of the types disclosed in these patents are limited both by their physical configuration and their reliance on the chemicals retained inside them for the pulsatile effect. Control over the intensity and spacing of the pulses which these devices can produce is limited, as is the number of pulses which can be delivered by a single device of reasonable dimensions. Reliability and predictability is also a problem in certain cases.
These and other limitations and disadvantages of known pulsatile delivery systems are addressed by the present invention.
Other literature of possible relevance to this invention are Simpson, B. E., et al., U.S. Pat. No. 4,416,659, issued Nov. 22, 1983; Edwards, S., et al., U.S. Pat. No. 4,867,980, issued Sept. 19, 1989; and LeFevre, R. J., et al., U.S. Pat. No. 4,997,420, issued Mar. 5, 1991. These patents disclose the use of coil springs in slow release capsules. The possible relevance of these patents will be evident form the description which follows: